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J Michael Cherry

Publications and source records attributed to J Michael Cherry.

At least 19 recordsLinked to original sources

The Saccharomyces Genome Database-a history of ideas and accomplishments, 1994-2026.

The Saccharomyces Genome Database (SGD) is one of the longest-running and most consequential biological databases in the world. Founded in the early 1990s at Stanford University under the visionary leadership of David Botstein and developed under the long-term technical direction of J. Michael Cherry, SGD has served for more than three decades not only as the authoritative knowledge center for the budding yeast Saccharomyces cerevisiae, but also as the source for much of the fundamentals of eukaryotic biology. This history traces the arc of a remarkable intellectual and scientific project: beginning with the challenge of building the very first integrated eukaryotic genome database and evolving across 30 years into a global knowledge hub for genetics, functional genomics, and human disease research. The history is organized chronologically, with each section highlighting the central ideas, technical developments, and concrete accomplishments of that period.

Databases, Genetic↗

Expanded protein information at SGD: new pages and proteome browser.

The recent explosion in protein data generated from both directed small-scale studies and large-scale proteomics efforts has greatly expanded the quantity of available protein information and has prompted the Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) to enhance the depth and accessibility of protein annotations. In particular, we have expanded ongoing efforts to improve the integration of experimental information and sequence-based predictions and have redesigned the protein information web pages. A key feature of this redesign is the development of a GBrowse-derived interactive Proteome Browser customized to improve the visualization of sequence-based protein information. This Proteome Browser has enabled SGD to unify the display of hidden Markov model (HMM) domains, protein family HMMs, motifs, transmembrane regions, signal peptides, hydropathy plots and profile hits using several popular prediction algorithms. In addition, a physico-chemical properties page has been introduced to provide easy access to basic protein information. Improvements to the layout of the Protein Information page and integration of the Proteome Browser will facilitate the ongoing expansion of sequence-specific experimental information captured in SGD, including post-translational modifications and other user-defined annotations. Finally, SGD continues to improve upon the availability of genetic and physical interaction data in an ongoing collaboration with BioGRID by providing direct access to more than 82,000 manually-curated interactions.

Computer Graphics↗

Tetrahymena Genome Database (TGD): a new genomic resource for Tetrahymena thermophila research.

We have developed a web-based resource (available at www.ciliate.org) for researchers studying the model ciliate organism Tetrahymena thermophila. Employing the underlying database structure and programming of the Saccharomyces Genome Database, the Tetrahymena Genome Database (TGD) integrates the wealth of knowledge generated by the Tetrahymena research community about genome structure, genes and gene products with the newly sequenced macronuclear genome determined by The Institute for Genomic Research (TIGR). TGD provides information curated from the literature about each published gene, including a standardized gene name, a link to the genomic locus in our graphical genome browser, gene product annotations utilizing the Gene Ontology, links to published literature about the gene and more. TGD also displays automatic annotations generated for the gene models predicted by TIGR. A variety of tools are available at TGD for searching the Tetrahymena genome, its literature and information about members of the research community.

Animals↗

Genome Snapshot: a new resource at the Saccharomyces Genome Database (SGD) presenting an overview of the Saccharomyces cerevisiae genome.

Sequencing and annotation of the entire Saccharomyces cerevisiae genome has made it possible to gain a genome-wide perspective on yeast genes and gene products. To make this information available on an ongoing basis, the Saccharomyces Genome Database (SGD) (http://www.yeastgenome.org/) has created the Genome Snapshot (http://db.yeastgenome.org/cgi-bin/genomeSnapShot.pl). The Genome Snapshot summarizes the current state of knowledge about the genes and chromosomal features of S.cerevisiae. The information is organized into two categories: (i) number of each type of chromosomal feature annotated in the genome and (ii) number and distribution of genes annotated to Gene Ontology terms. Detailed lists are accessible through SGD's Advanced Search tool (http://db.yeastgenome.org/cgi-bin/search/featureSearch), and all the data presented on this page are available from the SGD ftp site (ftp://ftp.yeastgenome.org/yeast/).

Chromosomes, Fungal↗

Saccharomyces cerevisiae S288C genome annotation: a working hypothesis.

The S. cerevisiae genome is the most well-characterized eukaryotic genome and one of the simplest in terms of identifying open reading frames (ORFs), yet its primary annotation has been updated continually in the decade since its initial release in 1996 (Goffeau et al., 1996). The Saccharomyces Genome Database (SGD; www.yeastgenome.org) (Hirschman et al., 2006), the community-designated repository for this reference genome, strives to ensure that the S. cerevisiae annotation is as accurate and useful as possible. At SGD, the S. cerevisiae genome sequence and annotation are treated as a working hypothesis, which must be repeatedly tested and refined. In this paper, in celebration of the tenth anniversary of the completion of the S. cerevisiae genome sequence, we discuss the ways in which the S. cerevisiae sequence and annotation have changed, consider the multiple sources of experimental and comparative data on which these changes are based, and describe our methods for evaluating, incorporating and documenting these new data.

Base Sequence↗

Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote.

The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance.

Animals↗

PatMatch: a program for finding patterns in peptide and nucleotide sequences.

Here, we present PatMatch, an efficient, web-based pattern-matching program that enables searches for short nucleotide or peptide sequences such as cis-elements in nucleotide sequences or small domains and motifs in protein sequences. The program can be used to find matches to a user-specified sequence pattern that can be described using ambiguous sequence codes and a powerful and flexible pattern syntax based on regular expressions. A recent upgrade has improved performance and now supports both mismatches and wildcards in a single pattern. This enhancement has been achieved by replacing the previous searching algorithm, scan_for_matches [D'Souza et al. (1997), Trends in Genetics, 13, 497-498], with nondeterministic-reverse grep (NR-grep), a general pattern matching tool that allows for approximate string matching [Navarro (2001), Software Practice and Experience, 31, 1265-1312]. We have tailored NR-grep to be used for DNA and protein searches with PatMatch. The stand-alone version of the software can be adapted for use with any sequence dataset and is available for download at The Arabidopsis Information Resource (TAIR) at ftp://ftp.arabidopsis.org/home/tair/Software/Patmatch/. The PatMatch server is available on the web at http://www.arabidopsis.org/cgi-bin/patmatch/nph-patmatch.pl for searching Arabidopsis thaliana sequences.

Arabidopsis↗

Inference of combinatorial regulation in yeast transcriptional networks: a case study of sporulation.

Decomposing transcriptional regulatory networks into functional modules and determining logical relations between them is the first step toward understanding transcriptional regulation at the system level. Modules based on analysis of genome-scale data can serve as the basis for inferring combinatorial regulation and for building mathematical models to quantitatively describe the behavior of the networks. We present here an algorithm called modem to identify target genes of a transcription factor (TF) from a single expression experiment, based on a joint probabilistic model for promoter sequence and gene expression data. We show how this method can facilitate the discovery of specific instances of combinatorial regulation and illustrate this for a specific case of transcriptional networks that regulate sporulation in the yeast Saccharomyces cerevisiae. Applying this method to analyze two crucial TFs in sporulation, Ndt80p and Sum1p, we were able to delineate their overlapping binding sites. We proposed a mechanistic model for the competitive regulation by the two TFs on a defined subset of sporulation genes. We show that this model accounts for the temporal control of the "middle" sporulation genes and suggest a similar regulatory arrangement can be found in developmental programs in higher organisms.

Algorithms↗

Fungal BLAST and Model Organism BLASTP Best Hits: new comparison resources at the Saccharomyces Genome Database (SGD).

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) is a scientific database of gene, protein and genomic information for the yeast Saccharomyces cerevisiae. SGD has recently developed two new resources that facilitate nucleotide and protein sequence comparisons between S.cerevisiae and other organisms. The Fungal BLAST tool provides directed searches against all fungal nucleotide and protein sequences available from GenBank, divided into categories according to organism, status of completeness and annotation, and source. The Model Organism BLASTP Best Hits resource displays, for each S.cerevisiae protein, the single most similar protein from several model organisms and presents links to the database pages of those proteins, facilitating access to curated information about potential orthologs of yeast proteins.

Databases, Genetic↗

GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.

SUMMARY: GO::TermFinder comprises a set of object-oriented Perl modules for accessing Gene Ontology (GO) information and evaluating and visualizing the collective annotation of a list of genes to GO terms. It can be used to draw conclusions from microarray and other biological data, calculating the statistical significance of each annotation. GO::TermFinder can be used on any system on which Perl can be run, either as a command line application, in single or batch mode, or as a web-based CGI script. AVAILABILITY: The full source code and documentation for GO::TermFinder are freely available from http://search.cpan.org/dist/GO-TermFinder/.

Abstracting and Indexing↗

Saccharomyces Genome Database (SGD) provides tools to identify and analyze sequences from Saccharomyces cerevisiae and related sequences from other organisms.

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/), a scientific database of the molecular biology and genetics of the yeast Saccharomyces cerevisiae, has recently developed several new resources that allow the comparison and integration of information on a genome-wide scale, enabling the user not only to find detailed information about individual genes, but also to make connections across groups of genes with common features and across different species. The Fungal Alignment Viewer displays alignments of sequences from multiple fungal genomes, while the Sequence Similarity Query tool displays PSI-BLAST alignments of each S.cerevisiae protein with similar proteins from any species whose sequences are contained in the non-redundant (nr) protein data set at NCBI. The Yeast Biochemical Pathways tool integrates groups of genes by their common roles in metabolism and displays the metabolic pathways in a graphical form. Finally, the Find Chromosomal Features search interface provides a versatile tool for querying multiple types of information in SGD.

Amino Acid Sequence↗

Saccharomyces genome database: underlying principles and organisation.

A scientific database can be a powerful tool for biologists in an era where large-scale genomic analysis, combined with smaller-scale scientific results, provides new insights into the roles of genes and their products in the cell. However, the collection and assimilation of data is, in itself, not enough to make a database useful. The data must be incorporated into the database and presented to the user in an intuitive and biologically significant manner. Most importantly, this presentation must be driven by the user's point of view; that is, from a biological perspective. The success of a scientific database can therefore be measured by the response of its users - statistically, by usage numbers and, in a less quantifiable way, by its relationship with the community it serves and its ability to serve as a model for similar projects. Since its inception ten years ago, the Saccharomyces Genome Database (SGD) has seen a dramatic increase in its usage, has developed and maintained a positive working relationship with the yeast research community, and has served as a template for at least one other database. The success of SGD, as measured by these criteria, is due in large part to philosophies that have guided its mission and organisation since it was established in 1993. This paper aims to detail these philosophies and how they shape the organisation and presentation of the database.

Databases, Nucleic Acid↗

SOURCE: a unified genomic resource of functional annotations, ontologies, and gene expression data.

The explosion in the number of functional genomic datasets generated with tools such as DNA microarrays has created a critical need for resources that facilitate the interpretation of large-scale biological data. SOURCE is a web-based database that brings together information from a broad range of resources, and provides it in manner particularly useful for genome-scale analyses. SOURCE's GeneReports include aliases, chromosomal location, functional descriptions, GeneOntology annotations, gene expression data, and links to external databases. We curate published microarray gene expression datasets and allow users to rapidly identify sets of co-regulated genes across a variety of tissues and a large number of conditions using a simple and intuitive interface. SOURCE provides content both in gene and cDNA clone-centric pages, and thus simplifies analysis of datasets generated using cDNA microarrays. SOURCE is continuously updated and contains the most recent and accurate information available for human, mouse, and rat genes. By allowing dynamic linking to individual gene or clone reports, SOURCE facilitates browsing of large genomic datasets. Finally, SOURCEs batch interface allows rapid extraction of data for thousands of genes or clones at once and thus facilitates statistical analyses such as assessing the enrichment of functional attributes within clusters of genes. SOURCE is available at http://source.stanford.edu.

Animals↗

Saccharomyces Genome Database (SGD) provides biochemical and structural information for budding yeast proteins.

The Saccharomyces Genome Database (SGD: http://genome-www.stanford.edu/Saccharomyces/) has recently developed new resources to provide more complete information about proteins from the budding yeast Saccharomyces cerevisiae. The PDB Homologs page provides structural information from the Protein Data Bank (PDB) about yeast proteins and/or their homologs. SGD has also created a resource that utilizes the eMOTIF database for motif information about a given protein. A third new resource is the Protein Information page, which contains protein physical and chemical properties, such as molecular weight and hydropathicity scores, predicted from the translated ORF sequence.

Amino Acid Motifs↗

A systematic approach to reconstructing transcription networks in Saccharomycescerevisiae.

Decomposing regulatory networks into functional modules is a first step toward deciphering the logical structure of complex networks. We propose a systematic approach to reconstructing transcription modules (defined by a transcription factor and its target genes) and identifying conditionsperturbations under which a particular transcription module is activateddeactivated. Our approach integrates information from regulatory sequences, genome-wide mRNA expression data, and functional annotation. We systematically analyzed gene expression profiling experiments in which the yeast cell was subjected to various environmental or genetic perturbations. We were able to construct transcription modules with high specificity and sensitivity for many transcription factors, and predict the activation of these modules under anticipated as well as unexpected conditions. These findings generate testable hypotheses when combined with existing knowledge on signaling pathways and protein-protein interactions. Correlating the activation of a module to a specific perturbation predicts links in the cell's regulatory networks, and examining coactivated modules suggests specific instances of crosstalk between regulatory pathways.

Gene Expression Profiling↗

Identification of unstable transcripts in Arabidopsis by cDNA microarray analysis: rapid decay is associated with a group of touch- and specific clock-controlled genes.

mRNA degradation provides a powerful means for controlling gene expression during growth, development, and many physiological transitions in plants and other systems. Rates of decay help define the steady state levels to which transcripts accumulate in the cytoplasm and determine the speed with which these levels change in response to the appropriate signals. When fast responses are to be achieved, rapid decay of mRNAs is necessary. Accordingly, genes with unstable transcripts often encode proteins that play important regulatory roles. Although detailed studies have been carried out on individual genes with unstable transcripts, there is limited knowledge regarding their nature and associations from a genomic perspective, or the physiological significance of rapid mRNA turnover in intact organisms. To address these problems, we have applied cDNA microarray analysis to identify and characterize genes with unstable transcripts in Arabidopsis thaliana (AtGUTs). Our studies showed that at least 1% of the 11,521 clones represented on Arabidopsis Functional Genomics Consortium microarrays correspond to transcripts that are rapidly degraded, with estimated half-lives of less than 60 min. AtGUTs encode proteins that are predicted to participate in a broad range of cellular processes, with transcriptional functions being over-represented relative to the whole Arabidopsis genome annotation. Analysis of public microarray expression data for these genes argues that mRNA instability is of high significance during plant responses to mechanical stimulation and is associated with specific genes controlled by the circadian clock.

Arabidopsis↗

Saccharomyces Genome Database (SGD) provides secondary gene annotation using the Gene Ontology (GO).

The Saccharomyces Genome Database (SGD) resources, ranging from genetic and physical maps to genome-wide analysis tools, reflect the scientific progress in identifying genes and their functions over the last decade. As emphasis shifts from identification of the genes to identification of the role of their gene products in the cell, SGD seeks to provide its users with annotations that will allow relationships to be made between gene products, both within Saccharomyces cerevisiae and across species. To this end, SGD is annotating genes to the Gene Ontology (GO), a structured representation of biological knowledge that can be shared across species. The GO consists of three separate ontologies describing molecular function, biological process and cellular component. The goal is to use published information to associate each characterized S.cerevisiae gene product with one or more GO terms from each of the three ontologies. To be useful, this must be done in a manner that allows accurate associations based on experimental evidence, modifications to GO when necessary, and careful documentation of the annotations through evidence codes for given citations. Reaching this goal is an ongoing process at SGD. For information on the current progress of GO annotations at SGD and other participating databases, as well as a description of each of the three ontologies, please visit the GO Consortium page at http://www.geneontology.org. SGD gene associations to GO can be found by visiting our site at http://genome-www.stanford.edu/Saccharomyces/.

Animals↗